CN104327095A - Preparation method of thieno- benzodiaxepin acidic salt - Google Patents
Preparation method of thieno- benzodiaxepin acidic salt Download PDFInfo
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Abstract
The invention discloses a preparation method of thieno- benzodiaxepin acidic salt, and the method is as follows: 1) in the catalysis of a basic ferric oxide / activated carbon catalyst, reacting 2-((2-nitrophenyl) amino)-5-methyl thiophene-3- carbonitrile with hydrazine hydrate, filtering, washing filter residue, merging washing liquid and filtrate to obtain a mixture liquid containing 2-((2- amino anilino)-5-methyl thiophene-3- carbonitrile; and 2) acidifying and heating for reflux of the mixture liquid to obtain the thieno- benzodiaxepin acidic salt. The preparation method of the thieno- benzodiaxepin acidic salt uses basic ferric oxide / activated carbon as the catalyst, has the advantages of low product preparation cost, high product purity and reaction yield, and the like, and is suitable for industrial production, and lays the foundation to improve the commercial preparation of ultimate products using the thieno- benzodiaxepin acidic salt as an intermediate.
Description
Technical field
The present invention relates to intermediate synthesis field, the invention still further relates to the preparation method of a kind of thieno--benzene diazepine acid-salt.
Background technology
Thieno--benzene diazepine acid-salt is the intermediate preparing olanzapine.There are some problems in the preparation method of discloseder thieno-s-benzene diazepine acid-salt.
US.Pat.No 5,229,382 reports the preparation method of 4-amino-2-methyl-10H thieno-[2,3-b] [1,5] benzene diazepine hydrochloride.Namely in acid condition by 2-(2-oil of mirbane amino)-5-thiotolene-3-nitrile Reduction with Stannous Chloride and cyclization obtains 4-amino-2-methyl-10H thieno-[2,3-b] [1,5] benzene diazepine hydrochloride.Owing to preparing 4-amino-2-methyl-10H thieno-[2,3-b] [1,5] tin protochloride is employed as reductive agent in benzene diazepine hydrochloride process, tin protochloride is expensive, be unsuitable for applying during business manufactures, and unreacted tin protochloride easily forms with product the complex compound being difficult to be separated, have impact on 4-amino-2-methyl-10H thieno-[2,3-b] [1,5] purity of benzene diazepine hydrochloride and preparation cost, finally causes finished product (as olanzapine) to be difficult to commercialization preparation.
Also the preparation method of thieno--benzene diazepine acid-salt is relate in CN200710041057.6, namely 2-(2-oil of mirbane is amino)-5-thiotolene-3-nitrile first uses iron powder reducing, then after filtering, in hydrochloric acid soln, reflux cyclization obtains 4-amino-2-methyl-10H thieno-[2,3-b] [1,5] benzene diazepine hydrochloride.The method adopts a large amount of iron powder to make reductive agent, need special conversion unit, and produce the serious scum of a large amount of environmental pollution, therefore the method is also difficult to industrially apply.
Summary of the invention
The object of the present invention is to provide a kind of relative low price of agents useful for same, pollute little thieno-the-preparation method of benzene diazepine acid-salt.
A preparation method for thieno--benzene diazepine acid-salt, comprises the following steps:
1) under the catalysis of alkali formula ferric oxide/activated-carbon catalyst, 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile shown in chemical formula 1 and hydrazine hydrate reaction, obtain the mixed solution comprising 2-(2-amido the anilino)-5-thiotolene-3-nitrile shown in chemical formula 2;
2) acidifying reflux mixed solution, obtains the thieno-shown in chemical formula 3-benzene diazepine acid-salt.
Further, step 1) in 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile and the reaction process of hydrazine hydrate be specially: 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile, alkali formula ferric oxide/activated-carbon catalyst, second alcohol and water are heated with stirring to 70 ~ 80 DEG C, drip hydrazine hydrate in 0.5 ~ 2 hour, continue reaction 1 ~ 4 hour.
Further, the mol ratio of 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile and hydrazine hydrate is 1: 1 ~ 3.
Further, step 2) in, in mixed solution, add hydrochloric acid, reflux 1 ~ 4 hour, steaming desolventizes, and filters after crystallisation by cooling, and filter cake water washing to pH5 ~ 6, then is drying to obtain after washing with acetone.
Further, the temperature of crystallisation by cooling is-5 ~ 20 DEG C, and drying temperature is 60 ~ 100 DEG C, and time of drying is 1 ~ 6 hour.
Further, alkali formula ferric oxide/activated-carbon catalyst is prepared by following steps:
A) iron(ic) chloride is soluble in water, add gac, dry at 20 ~ 60 DEG C, obtain iron trichloride/Mixture of Activated Carbon, the mass ratio of iron(ic) chloride, water and gac is 1: 2 ~ 10: 1 ~ 5;
B) iron trichloride/Mixture of Activated Carbon is joined in ammoniacal liquor stir, after having reacted, filter, wash solid with water to pH7 ~ 8, drying solid, obtain alkali formula ferric oxide/activated-carbon catalyst.
Further, in step b) in, gac is added ferric chloride Solution, floods 0.5 ~ 5 hour.
Further, in step b) in, add ammoniacal liquor in 0 ~ 60 DEG C of stirring reaction 1 ~ 10 hour.
Further, the concentration of ammoniacal liquor is 5 ~ 15%, and the ratio of ammoniacal liquor and gac is 1 ~ 10: 1.
Further, step b) in water be the water of 0 ~ 40 DEG C, in drying solid, by solid at 120 DEG C dry 4 hours.
The present invention has following beneficial effect: the preparation method of thieno-of the present invention-benzene diazepine acid-salt, adopt alkali formula ferric oxide/carbon compositing catalyst, the preparation cost with product is low, the purity of product and reaction yield advantages of higher, is suitable for industrial production.
Except object described above, feature and advantage, the present invention also has other object, feature and advantage.Below with reference to figure, the present invention is further detailed explanation.
Accompanying drawing explanation
The accompanying drawing forming a application's part is used to provide a further understanding of the present invention, and schematic description and description of the present invention, for explaining the present invention, does not form inappropriate limitation of the present invention.In the accompanying drawings:
Fig. 1 is the schema of the preparation method of the alkali formula ferric oxide/activated-carbon catalyst of the preferred embodiment of the present invention;
Fig. 2 is the schema of the preparation method of the thieno--benzene diazepine acid-salt of the preferred embodiment of the present invention.
Embodiment
Below in conjunction with accompanying drawing, embodiments of the invention are described in detail, but the multitude of different ways that the present invention can be defined by the claims and cover is implemented.
With reference to Fig. 1, the preferred embodiments of the present invention provide a kind of preparation method of alkali formula ferric oxide/activated-carbon catalyst, comprise the following steps:
S01: iron(ic) chloride is soluble in water, adds gac, and dry at 20 ~ 60 DEG C, obtain iron trichloride/Mixture of Activated Carbon, the mass ratio of iron(ic) chloride, water and gac is 1: 2 ~ 10: 1 ~ 5.
S02: iron trichloride/Mixture of Activated Carbon is joined in ammoniacal liquor and stirred, after having reacted, filters, washes solid with water to pH7 ~ 8, drying solid, obtain alkali formula ferric oxide/activated-carbon catalyst.
The mass ratio of iron(ic) chloride, water and gac is preferably 1: 2 ~ 10: 1 ~ 5.Deionized water is very few, and iron(ic) chloride is not easy to dissolve, and gac and iron(ic) chloride mixing inequality, can not fully contact; And deionized water is too much, after the ferric chloride Solution after dissolving mixes with gac, much iron(ic) chloride is also had not to be tightly held by activated carbon, simultaneously because the water yield cannot be dried too much, cannot be dry at low temperatures, obtained catalyst effect is poor.When the amount of gac is very few, iron(ic) chloride can not be adsorbed in activated carbon surface preferably, and the effect of catalyzer is poor, and when the amount of gac is too much, in the catalyzer of unit weight, iron(ic) chloride is very few, and the catalytic effect of catalyzer is not good yet.More excellent, the mass ratio of iron(ic) chloride, water and gac is 1: 73: 4.9.When iron(ic) chloride is dissolved in deionized water, iron(ic) chloride can be dissolved in portions of de-ionized water, then add remaining deionized water.In addition iron(ic) chloride also can adopt Iron trichloride hexahydrate (FeCl
3.6H
2o).
Gac can be ground to suitable particle size range before adding iron(ic) chloride mixed solution, also after gac can being added iron(ic) chloride mixed solution, grind together with iron(ic) chloride mixed solution, a kind of mode after being preferably, gac adds in iron(ic) chloride mixed solution and grinds, in process of lapping, gac contacts more abundant with iron(ic) chloride, and iron(ic) chloride is more easily adsorbed on gac.
Gac adds ferric chloride Solution, and the process of charcoal absorption iron(ic) chloride is comparatively slow, floods and within 0.5 ~ 5 hour, can ensure that iron(ic) chloride is adsorbed in gac preferably.More excellent dipping time is 1 hour, after flooding latter 1 hour, dries, obtain iron trichloride/Mixture of Activated Carbon at 20 ~ 60 DEG C.More excellent bake out temperature is 40 DEG C, when bake out temperature is too high, iron(ic) chloride is migrated to activated carbon surface in high-temperature drying procedures, greatly reduce the useful area that iron(ic) chloride is tightly held by activated carbon, iron(ic) chloride is converted to FeO (OH), the useful area be tightly held by activated carbon also greatly reduces, and the catalysis efficiency of alkali formula ferric oxide/activated-carbon catalyst (FeO (OH)/C) reduces greatly; And bake out temperature too low time, drying rate is comparatively slow, and drying effect is poor.
Iron trichloride/Mixture of Activated Carbon is joined in ammoniacal liquor and stirs, is preferably 0 ~ 60 DEG C of stirring reaction 1 ~ 10 hour, carries out to react fully, improve reaction yield.
After iron trichloride/Mixture of Activated Carbon and ammoniacal liquor have reacted, filter, the deionized water wash of 60 ~ 100 DEG C need be adopted, otherwise filtration velocity is slow, affects production efficiency.Washing needs fully washing, and fully to wash away ammonia, when avoiding alkali formula ferric oxide/activated-carbon catalyst to use, ammonia affects reduzate quality.After washing, by solid at 120 DEG C dry 4 hours, remove the water in solid, obtain FeO (OH)/C catalyst.Under the high temperature of 100 ~ 120 DEG C, drying can make catalyst activation, has maximum catalytic activity, otherwise weak effect.
The preparation method of alkali formula ferric oxide/activated-carbon catalyst of the present invention, the ammoniacal liquor of low concentration can be adopted, the concentration adopting ammoniacal liquor is 5 ~ 15%, be preferably the ammoniacal liquor of 10%, and decrease the consumption of ammoniacal liquor, the ratio of ammoniacal liquor and described gac is preferably 1 ~ 10: 1, more excellent is 3: 1, just can meet reaction requirement, ammoniacal liquor can Reusability, reduces cost.
With reference to Fig. 2, the preferred embodiments of the present invention provide the preparation method of a kind of thieno--benzene diazepine acid-salt, comprise the following steps:
S11: under the catalysis of alkali formula ferric oxide/activated-carbon catalyst, 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile and hydrazine hydrate reaction, obtain the mixed solution comprising 2-(2-amido anilino)-5-thiotolene-3-nitrile.
S12: acidifying reflux mixed solution, obtains thieno--benzene diazepine acid-salt.
Reaction equation is as follows:
2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile (chemical formula 1), alkali formula ferric oxide/activated-carbon catalyst, second alcohol and water are heated with stirring to 70 ~ 75 DEG C, hydrazine hydrate is dripped in 1 hour, continue reaction 3 hours, be preferably 2 hours, obtain intermediate product 2-(2-amido the anilino)-5-thiotolene-3-nitrile shown in chemical formula 2.Reaction filtered while hot, washs filter residue with hot ethanol, merges washings and filtrate, obtains mixed solution.The mol ratio of 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile and hydrazine hydrate is preferably 1: 1 ~ 3, and more excellent is 1: 2.0.Intermediate product 2-(2-amido anilino)-5-thiotolene-3-nitrile carries out simple separation and purifying by filtering.
Acidifying reflux mixed solution, obtains thieno--benzene diazepine acid-salt.Mixed solution preferably adds hcl acidifying, is specially and adds hydrochloric acid in mixed solution, reflux 1 ~ 4 hour, and be preferably 2 hours, steaming desolventizes, and filters after crystallisation by cooling, and filter cake water washing to pH5 ~ 6, then uses washing with acetone filter cake, dry cake and get final product.The temperature of reflux is preferably 70 ~ 100 DEG C, and more excellent is 86 DEG C, and steam and desolventize to 95 DEG C, the temperature of crystallisation by cooling is-5 ~ 20 DEG C °, and be preferably 0 DEG C, drying temperature is 60 ~ 100 DEG C, and be preferably 80 DEG C, time of drying is 1 ~ 6 hour, is preferably 4 hours.
Embodiment 1
The preparation of alkali formula ferric oxide/activated-carbon catalyst: take 6.8g FeCl
3.6H
2o, is put in beaker, first adds a small amount of deionized water to FeCl
3quan Rong, then add remaining deionized water (amounting to 30mL), mix, then the gac of 20.0g is added in this solution, grind 1 hour, then in 40 DEG C of oven dry, obtain the FeCl flooded
3/ C.By FeCl under stirring
3/ C adds in the ammoniacal liquor of 70mL 10%, in stirring at room temperature 4h.Filter, fully wash solid to pH7 with 80 DEG C of deionized waters, in 120 DEG C of dry 4h, grind broken, obtain FeO (OH)/C.
The preparation of thieno--benzene diazepine acid-salt: by 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile (10.0g, 0.038mol), alkali formula ferric oxide/activated-carbon catalyst (1.0g), ethanol (60mL) and water (20mL) add in reaction flask successively, be heated with stirring to 75 DEG C, hydrazine hydrate (4.8g is slowly dripped in 1 hour, 0.076mol), 75 DEG C of reaction 2h are continued at after adding.Filtered while hot, with appropriate hot ethanol washing filter residue, and adds 6mol.L to filtrate
-1hydrochloric acid (65mL), after reflux 2h, steaming desolventizes, 0 DEG C of crystallisation by cooling 5h, filter, filter cake first washs to pH5 by suitable quantity of water, then is faint yellow by washing with acetone to washing lotion, 80 DEG C of dry 4h, obtain brown color or yellow crystalline powder [4-amino-2-methyl-10H-thieno-[2,3-b] [1,5]-benzene diazepine hydrochloride] 8.7g, yield is 85.0%, m.p. > 250 DEG C.
Embodiment 2
The preparation of alkali formula ferric oxide/activated-carbon catalyst: take 3.0g FeCl
3.6H
2o, is put in beaker, first adds a small amount of deionized water to FeCl
3quan Rong, then add remaining deionized water (amounting to 30mL), mix, then the gac of 15.0g is added in this solution, dry at 20 DEG C after 0.5 hour, obtain the FeCl flooded
3/ C.By FeCl under stirring
3/ C adds in the ammoniacal liquor of 60mL 5%, stirs 1h in 0.Filter, fully wash solid to pH7 with 60 DEG C of deionized waters, in 100 DEG C of dry 3h, grind broken, obtain FeO (OH)/C.
The preparation of thieno--benzene diazepine acid-salt: by 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile (10.0g, 0.038mol), alkali formula ferric oxide/activated-carbon catalyst (1.0g), ethanol (60mL) and water (20mL) add in reaction flask successively, be heated with stirring to 70 DEG C, hydrazine hydrate (2.4g is slowly dripped in 0.5 hour, 0.038mol), 75 DEG C of reaction 1h are continued at after adding.Filtered while hot, with appropriate hot ethanol washing filter residue, and adds 6mol.L to filtrate
-1hydrochloric acid (65mL), after reflux 1h, steaming desolventizes,-5 DEG C of crystallisation by cooling 5h, filter, filter cake first washs to pH6 by suitable quantity of water, then is faint yellow by washing with acetone to washing lotion, 60 DEG C of dry 1h, obtain brown color or yellow crystalline powder [4-amino-2-methyl-10H-thieno-[2,3-b] [1,5]-benzene diazepine hydrochloride] 8.4g, yield is 82.0%, m.p. > 250 DEG C.
Embodiment 3
The preparation of alkali formula ferric oxide/activated-carbon catalyst: take 3.0g FeCl
3, be put in beaker, first add a small amount of deionized water to FeCl
3quan Rong, then add remaining deionized water (amounting to 30mL), mix, then this solution is added in the gac of 15.0g, grind 3 hours, then in 40 DEG C of oven dry, obtain the FeCl flooded
3/ C.By FeCl under stirring
3/ C adds in the ammoniacal liquor of 60mL 12%, in stirring at room temperature 6h.Filter, fully wash solid to pH7.5 with 70 DEG C of deionized waters, in 115 DEG C of dry 4h, grind broken, obtain FeO (OH)/C.
The preparation of thieno--benzene diazepine acid-salt: by 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile (10.0g, 0.038mol), alkali formula ferric oxide/activated-carbon catalyst (1.0g), ethanol (60mL) and water (20mL) add in reaction flask successively, be heated with stirring to 75 DEG C, hydrazine hydrate (4.8g is slowly dripped in 1.5 hours, 0.076mol), 78 DEG C of reaction 2h are continued at after adding.Filtered while hot, with appropriate hot ethanol washing filter residue, and adds 6mol.L to filtrate
-1hydrochloric acid (65mL), after reflux 3h, steaming desolventizes, 15 DEG C of crystallisation by cooling 5h, filter, filter cake first washs to pH6 by suitable quantity of water, then is faint yellow by washing with acetone to washing lotion, 80 DEG C of dry 4h, obtain brown color or yellow crystalline powder [4-amino-2-methyl-10H-thieno-[2,3-b] [1,5]-benzene diazepine hydrochloride] 8.3g, yield is 81.0%, m.p. > 250 DEG C.
Embodiment 4
The preparation of alkali formula ferric oxide/activated-carbon catalyst: take 6.7g FeCl
3, be put in beaker, first add a small amount of deionized water to FeCl
3quan Rong, then add remaining deionized water (amounting to 40mL), mix, then this solution is added in the gac of 26.7g, grind 1 hour, then in 60 DEG C of oven dry, obtain the FeCl flooded
3/ C.By FeCl under stirring
3/ C adds in the ammoniacal liquor of 60mL 10%, in stirring at room temperature 10h.Filter, fully wash solid to pH8 with 85 DEG C of deionized waters, in 120 DEG C of dry 5h, grind broken, obtain FeO (OH)/C.
The preparation of thieno--benzene diazepine acid-salt: by 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile (10.0g, 0.038mol), alkali formula ferric oxide/activated-carbon catalyst (1.0g), ethanol (60mL) and water (20mL) add in reaction flask successively, be heated with stirring to 80 DEG C, hydrazine hydrate (4.8g is slowly dripped in 2 hours, 0.076mol), 80 DEG C of reaction 4h are continued at after adding.Filtered while hot, with appropriate hot ethanol washing filter residue, and adds 6mol.L to filtrate
-1hydrochloric acid (65mL), after reflux 4h, steaming desolventizes, 20 DEG C of crystallisation by cooling 5h, filter, filter cake first washs to pH6 by suitable quantity of water, then is faint yellow by washing with acetone to washing lotion, 100 DEG C of dry 6h, obtain brown color or yellow crystalline powder [4-amino-2-methyl-10H-thieno-[2,3-b] [1,5]-benzene diazepine hydrochloride] 8.5g, yield is 83.0%, m.p. > 250 DEG C.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, for a person skilled in the art, the present invention can have various modifications and variations.Within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. a preparation method for thieno--benzene diazepine acid-salt, is characterized in that, comprise the following steps:
1) under the catalysis of alkali formula ferric oxide/activated-carbon catalyst, 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile shown in chemical formula 1 and hydrazine hydrate reaction, obtain the mixed solution comprising 2-(2-amido the anilino)-5-thiotolene-3-nitrile shown in chemical formula 2;
2) mixed solution described in acidifying reflux, obtains the thieno-shown in chemical formula 3-benzene diazepine acid-salt.
2. the preparation method of thieno-according to claim 1-benzene diazepine acid-salt, it is characterized in that, described step 1) in 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile and the reaction process of hydrazine hydrate be specially: described 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile, described alkali formula ferric oxide/activated-carbon catalyst, second alcohol and water are heated with stirring to 70 ~ 80 DEG C, drip described hydrazine hydrate in 0.5 ~ 2 hour, continue reaction 1 ~ 4 hour.
3. the preparation method of thieno-according to claim 2-benzene diazepine acid-salt, is characterized in that, the mol ratio of described 2-(2-oil of mirbane amido)-5-thiotolene-3-nitrile and described hydrazine hydrate is 1: 1 ~ 3.
4. the preparation method of thieno-according to claim 2-benzene diazepine acid-salt, it is characterized in that, described step 2) in, hydrochloric acid is added in described mixed solution, reflux 1 ~ 4 hour, steaming desolventizes, and filters after crystallisation by cooling, filter cake water washing to pH5 ~ 6, then is drying to obtain after washing with acetone.
5. the preparation method of thieno-according to claim 4-benzene diazepine acid-salt, is characterized in that, the temperature of described crystallisation by cooling is-5 ~ 20 DEG C, and described drying temperature is 60 ~ 100 DEG C, and described time of drying is 1 ~ 6 hour.
6. the preparation method of the thieno-according to any one of Claims 1 to 5-benzene diazepine acid-salt, is characterized in that, described alkali formula ferric oxide/activated-carbon catalyst is prepared by following steps:
A) iron(ic) chloride is soluble in water, add gac, dry at 20 ~ 60 DEG C, obtain iron trichloride/Mixture of Activated Carbon, the mass ratio of described iron(ic) chloride, water and gac is 1: 2 ~ 10: 1 ~ 5;
B) described iron trichloride/Mixture of Activated Carbon is joined in ammoniacal liquor stir, after having reacted, filter, wash solid with water to pH7 ~ 8, drying solid, obtain alkali formula ferric oxide/activated-carbon catalyst.
7. the preparation method of thieno-according to claim 6-benzene diazepine acid-salt, is characterized in that, at described step b) in, described gac is added ferric chloride Solution, floods 0.5 ~ 5 hour.
8. the preparation method of thieno-according to claim 6-benzene diazepine acid-salt, is characterized in that, at described step b) in, add described ammoniacal liquor in 0 ~ 60 DEG C of stirring reaction 1 ~ 10 hour.
9. the preparation method of thieno-according to claim 7-benzene diazepine acid-salt, is characterized in that, the concentration of described ammoniacal liquor is 5 ~ 15%, and the ratio of described ammoniacal liquor and described gac is 1 ~ 10: 1.
10. the preparation method of thieno-according to claim 6-benzene diazepine acid-salt, is characterized in that, described step b) in water be the water of 0 ~ 40 DEG C, in described drying solid, by solid at 100 ~ 120 DEG C dry 3 ~ 5 hours.
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| WO2021224830A1 (en) * | 2020-05-05 | 2021-11-11 | Syneurx International (Taiwan) Corp. | Salts of neuroceuticals and uses thereof |
| WO2023098592A1 (en) * | 2021-11-30 | 2023-06-08 | 奥锐特药业股份有限公司 | Preparation method for carbon-loaded iron-based catalyst and use thereof in synthesis of intermediates of anti-cancer inhibitors |
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| CN101311179A (en) * | 2007-05-23 | 2008-11-26 | 华东理工大学 | Improved process for preparing thieno-benzodiazepine compounds |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2021224830A1 (en) * | 2020-05-05 | 2021-11-11 | Syneurx International (Taiwan) Corp. | Salts of neuroceuticals and uses thereof |
| WO2023098592A1 (en) * | 2021-11-30 | 2023-06-08 | 奥锐特药业股份有限公司 | Preparation method for carbon-loaded iron-based catalyst and use thereof in synthesis of intermediates of anti-cancer inhibitors |
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Application publication date: 20150204 |